Vitamin D and the Brain
Is vitamin D required for normal brain development?
Yes, Professor John McGrath and Dr. Darryl Eyles of the University of Queensland in Australia have repeatedly warned us that normal brain development depends on adequate amounts of activated vitamin D to orchestrate the cellular architecture of the brain. Both the vitamin D receptor and the enzyme necessary to make activated vitamin D are present in a wide-variety of human brain tissues very early in pregnancy. Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin D3 and brain development. Neuroscience. 2003;118(3):641–53. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005 Jan;29(1):21–30.
Production of the vitamin D receptor in the developing mammalian brain rises steadily beginning several weeks after conception where activated vitamin D induces the expression of nerve growth factor and stimulates brain cell growth. McGrath JJ, Feron FP, Burne TH, Mackay-Sim A, Eyles DW. Vitamin D3—implications for brain development. J Steroid Biochem Mol Biol. 2004 May;89–90(1–5):557–60. Brachet P, et al. Vitamin D, a neuroactive hormone: from brain development to pathological disorders. In Feldman D, Pike JW, Glorieux FH, eds. Vitamin D. San Diego: Elsevier, 2005.
We do not know what vitamin D deficiency during pregnancy does to human brains, but we know what it does to rat brains and it is not good. In a series of recent animal experiments, Professor John McGrath, Dr. Darryl Eyles and their Australian group found severe maternal vitamin D deficiency in mother rats produced babies with abnormal apoptosis (normal cell death) and abnormal brain cell proliferation, reduced production of proteins involved in nerve structure, and baby rats who have subtle abnormalities in both learning and memory. Ko P, Burkert R, McGrath J, Eyles D. Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cycle during rat brain development. Brain Res Dev Brain Res. 2004 Oct 15;153(1):61–8. Feron F, et al. Developmental Vitamin D3 deficiency alters the adult rat brain. Brain Res Bull. 2005 Mar 15;65(2):141–8. Burne TH, et al. Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav Brain Res. 2004 Oct 5;154(2):549–55. Becker A, et al. Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats. Behav Brain Res. 2005 Jun 20;161(2):306–12.
Several months ago, Dr. Almeras, Professor Feron, and their group at the University of the Mediterranean in Marseilles found developmental vitamin D deficiency disrupts 36 proteins involved in mammalian brain development. Severe maternal vitamin D deficiency leads to rat pups with increased brain size and enlarged ventricles (chambers in the brain), abnormalities very similar to those found in autistic children. Almeras L, et al. Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics. 2007 Mar;7(5):769–80. Piven J, et al. An MRI study of brain size in autism. Am J Psychiatry. 1995 Aug;152(8):1145–9.
Abnormal inflammation is associated with both autism and vitamin D deficiency. For example, autistic individuals show increases in cytokines (inflammatory mediators) that show a striking similarity to the immune processes regulated by vitamin D. Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006 Jul;80(1):1–15. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1717S–20S.
Both the brain and the blood of autistic individuals show evidence of ongoing chronic inflammation and oxidative stress. That is, the autistic disease process is progressive and probably increasingly destructive. If this ongoing inflammation could be interrupted, the symptoms might improve. Hope for a vitamin D treatment effect lies in activated vitamin D's powerful anti-inflammatory properties. Its administration decreases production of inflammatory cytokines in the brain, which have consistently been associated with brain impairment. Activated vitamin D stimulates neurotrophin release (neurotrophins induce the survival of nerve cells), reduces toxic calcium levels in the brain, and inhibits the production of nitrous oxide (nitrous oxide destroys brain cells). Besides reducing inflammatory cytokines, vitamin D does one more thing: it increases concentrations of glutathione—the brain's master antioxidant. Moore ME, Piazza A, McCartney Y, Lynch MA. Evidence that vitamin D3 reverses age-related inflammatory changes in the rat hippocampus. Biochem Soc Trans. 2005 Aug;33(Pt 4):573–7. Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A. Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels. Nephrol Dial Transplant. 2006 Apr;21(4):889–97. Kalueff AV, Eremin KO, Tuohimaa P. Mechanisms of neuroprotective action of vitamin d(3). Biochemistry (Mosc). 2004 Jul;69(7):738–41. Garcion E, et al. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002 Apr;13(3):100–5. Chen KB, Lin AM, Chiu TH. Systemic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain. Ann N Y Acad Sci. 2003 May;993:313–24; discussion 345–9.
At least 5 studies have found significant associations between higher vitamin D levels and better intellectual functioning, but they all studied adults. However, a recent report found a very high incidence of vitamin D deficiency among 337 younger individuals with intellectual disabilities. The obvious explanation is that intellectually impaired individuals do not go outdoors as often as higher functioning individuals and thus have lower vitamin D levels. Two groups found the association after controlling for outdoor activities, making it likely that low vitamin D levels per se impair intellectual ability. Dhesi JK, Bearne LM, Moniz C, Hurley MV, Jackson SH, Swift CG, Allain TJ. Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status. J Bone Miner Res. 2002 May;17(5):891–7. Kenny AM, Biskup B, Robbins B, Marcella G, Burleson JA. Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men. J Am Geriatr Soc. 2003 Dec;51(12):1762–7. Kipen E, Helme RD, Wark JD, Flicker L. Bone density, vitamin D nutrition, and parathyroid hormone levels in women with dementia. J Am Geriatr Soc. 1995 Oct;43(10):1088–91. Vanlint S, Nugent M. Vitamin D and fractures in people with intellectual disability. J Intellect Disabil Res. 2006 Oct;50(Pt 10):761–7. Flicker L, Mead K, MacInnis RJ, Nowson C, Scherer S, Stein MS, Thomasx J, Hopper JL, Wark JD. Serum vitamin D and falls in older women in residential care in Australia. J Am Geriatr Soc. 2003 Nov;51(11):1533–8. Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007 Apr 15;460(2):202–5.
Vitamin D's role in increasing glutathione levels may explain the link between mercury and other heavy metals, oxidative stress, and autism. For example, activated vitamin D lessens heavy metal induced oxidative injuries in rat brain. The primary route for brain toxicity of most heavy metals is through depletion of glutathione. Besides its function as a master antioxidant, glutathione acts as a chelating (binding) agent to remove heavy metals such as mercury. Autistic individuals have difficulty excreting heavy metals like mercury. If brain levels of activated vitamin D are too low to employ glutathione properly, and thus unable to remove heavy metals, they may be damaged by heavy metal loads normal children easily excrete. That is, the mercury in Thiomerosol vaccines may have injured vitamin D deficient children while normal children would have easily bound the mercury and excreted it. These studies offer further hope that sun-exposure or vitamin D supplements may help autistic children by increasing glutathione and removing heavy metals. Not only do we have more clues that vitamin D is involved in autism, the vitamin D theory just did something else: it explained two other theories of autism, the mercury accumulation theory and the oxidative stress theory. Lin AM, Chen KB, Chao PL. Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS. Ann N Y Acad Sci. 2005 Aug;1053:319–29. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12(10):1161–208. Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J Toxicol Environ Health B Crit Rev. 2006 Nov–Dec;9(6):485–99.
It bears repeating that the amount of activated vitamin D in the brain directly depends on the amount of vitamin D made in the skin, or ingested orally.» page: autism index 1 2 3 4 5 6 7 8 9 10 11